Background of this medicine

When early drug developers were trying to get an effective drug from the Yew tree, separating the chemical fractions from the bark samples was a difficult and slow process. It required skill and intuition by the researchers, using equipment that can now be found only in museums.

Research on the extracted chemicals was arduous and nearly every chemical turned out to be so toxic to humans that it killed every cell, not just cancerous ones. One promising compound needed a name long before its structure was determined. They simply named it from the source, “Taxus” with the ending for alcohol, “ol” without any real consideration. “Taxol” was found to have already been trademarked in the 1930’s by a French company for a laxative product. However, the drug company Bristol Myers Squibb was able to purchase the trademark and convince the Patent and Trademark office that a common laxative trademark should now apply to an anticancer drug.

Research was very slow. Supply was a challenge because the Yew tree was rare and grew very slowly. Paclitaxel solubility in water was described by one researcher as being equivalent to that of brick dust. It was not clear that Taxol could be administered to patients. Severe hypersensitivity in some clinical patients and failures as an anti-leukemic drug nearly stopped research on this chemical.

By 1971 scientists had established that Taxol displayed some promise as an anticancer agent. However, there was great reluctance to even harvest enough for clinical trials. The Pacific Yew tree is not common. Each tree could supply about 2 kilograms of bark. 12 kilograms of bark was needed to produce one half gram of Taxol. The Yew tree dies after stripping the bark.

In 1977, an order for 7,000 pounds of bark was made. This meant killing 1,500 trees, scattered in patches over millions of acres of old growth forests in the Pacific Northwest. This coincided with and became enmeshed in the debate over the spotted owl habitat. The need for natural remedies and medicinal herbs conflicted with conservationists and brought considerable notoriety to Taxol.

ground up tree bark
Ground-up Yew Tree Bark, in days when paclitaxel was made from bark.
Pulic domain Source: Mike Trumball, Hauser Northwest

Paclitaxel was found to promote regression of mammary tumors in 1978. The next year, it was found that the Paclitaxel mechanism was unique. Older anti-cancer compounds killed cancer cells by inhibiting the production of the building blocks that are needed for the cell to divide. Paclitaxel stimulates the production of the building blocks such that the cells cannot coordinate cell division. In the cell division cycle, it works in the G2 (Gap 2) and M phases, by stabilizing microtubules and inhibiting their disassembly. This essentially stops cell reproduction, and slows the growth of cancer. When the drug gets inside the reproducing cell, it can distort mitotic spindles, causing chromosomes to break.

The drug showed great success in cases of metastatic breast cancer. In 1992 the FDA approved the drug and Bristol-Myers Squib put it on the market at a wholesale price of just under $1000 for each dose. (Patients typically got 4 or 5 doses per year.) At the time, it was the most expensive drug on the market, although compared to some of today's drugs, it was relatively cheap.

Who knows - there may be numerous anti-cancer agents yet to be discovered from plant, marine, and fungal sources. Cancer is not a single disease. It is several hundred diseases and will almost certainly require many agents for treatment. The Taxol story shows the utility of searching for highly active natural products. It was a successful business venture as well as a medical success, saving many lives.

Note: In 2011 the International Union for Conservation of Nature designated a species of Asian Yew Tree used to harvest paclitaxel as endangered.

Treatment with paclitxel.

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